Blages

Saturday, October 16, 2010

Genomic Imprinting II: Inclusive Fitness and Conflict

So, as we discussed previously, genomic imprinting is the phenomenon where the pattern of expression of an allele differs depending on whether that allele was inherited from your mother or your father. This difference in expression does not depend on differences in the DNA sequence of the two alleles. Your two alleles might have identical DNA sequences, but function completely differently.

For example, one of the two alleles might be epigenetically silenced. That is, because of reversible chemical modifications to the DNA, or to proteins that are closely associated with the DNA, that allele would be inactive. The other allele, with an identical DNA sequence, but different modifications, would be happily chugging along producing its gene product(s). Today's question is, "That seems crazy! Why would you do something like that?"

One of interesting (and by "interesting" I mean "sad") things about evolutionary biologists is that whenever something genuinely new and surprising is found in the world, everyone feels the need to propose an evolutionary explanation for it, whether new explanations are needed or not. So, many attempts to explain the origins of imprinting have been proposed, most of which are consistent with at least some of the data, and a few of which actually make sense. There is one explanation, however, that is far and away the most successful in explaining the distribution and nature of imprinted genes: the "Kinship" or "conflict" theory of imprinting. This theory owes its creation and early development primarily to David Haig (who laid out the theory originally in papers with Mark Westoby and Tom Moore).

The basic idea of the Kinship Theory is that natural selection favors different expression behaviors for maternally and paternally inherited alleles. That is, the optimal level of expression for an allele that is maternally inherited is different from the optimal level for a paternally inherited allele. Now, if you think about that for a minute, it probably seems strange. I mean, if I survive and reproduce, that's equally good for any of my genes, independent of where I got them from, right? Right?

The key is recognizing that natural selection favors allele that pass on the largest number of copies to future generations. ("Isn't that what I just said?") AND, that it doesn't matter whether those copies are passed on directly by my having children, or if they are passed on because because one of my relatives, who has inherited an identical copy of that allele, has children. There are different ways to represent this (which are all mathematically equivalent if you do them right), but the one that I find most intuitive is the idea of "inclusive fitness." Basically, we can think of natural selection as maximizing the inclusive fitness of an allele, which is the fitness of every individual in the population, weighted by the probability that they carry the allele. In the simplest model, this probability is 1 for me, 1/2 for a sibling, 1/8 for a cousin, and so on.

Now, think about your relatives. With the exception of your descendants, your full siblings, and their descendants, all of your relatives are related to you either through your mother or your father. That means that, in general, this inclusive fitness calculation will be different for maternally and paternally derived alleles. Therefore, there will be a conflict, where the phenotype that would maximize the inclusive fitness of your maternally inherited allele will be different from the one that would maximize the inclusive fitness of your paternally inherited allele. If this difference is large enough, it can actually drive alleles to take on two different conditional expression strategies, and, voila, imprinting.

Granted, even in the most extreme cases, this difference is likely to be pretty subtle, which might make it seem strange that this could explain a situation where one of the two alleles is completely turned off, while the other one is cranking away. This phenomenon, where a little conflict leads to a big effect, will be the subject of the next installment.

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